The cutaneous circulation is one of the most variable and has the potential for very high levels of blood flow. Its control is important both to temperature regulation and to hemodynamics and blood pressure regulation generally. The mechanisms for that control in humans are gaining clarity. In the recent history of the laboratory, we have made several important findings. We have shown clearly that, in women, control of both the adrenergic vasoconstrictor and the nonadrenergic active vasodilator systems are subject to modification by reproductive hormone status such that body temperature and its control are shifted to higher levels when estrogen and progesterone are elevated. We also know that important control of the cutaneous circulation derives not only from thermoregulatory reflexes, but also from baroreceptor reflexes and the reflexes associated with dynamic exercise, i.e., nonthermoregulatory reflexes. Third, we found that the sympathetic vasoconstrictor control and the active vasodilator control of the cutaneous circulation each have both primary transmitters and co-transmitters involved in their vasomotor functions. We have strong evidence that NPY has an important co-transmitter role in the reflex vasoconstrictor responses to body cooling and that VIP has an important role as a cholinergic co-transmitter in the active vasodilator response to body warming. We propose to draw these elements of control together, by seeking to discover whether the cyclic variation in vasoconstrictor control during the menstrual cycle is via the sympathetic co-transmitter NPY; similarly, whether there is a hormonally associated shift in the role for the co-transmitter in the vasodilator system (VIP). We also seek to discover the roles for sympathetic co-transmitters in the influence of nonthermoregulatory reflexes on cutaneous vascular control, specifically, in response to the onset of exercise, in the inhibition of the increase in skin blood flow as exercise continues and when blood pressure is challenged by simulated hemorrhage. Lastly, we will test for a functional role for sympathetic transmitters other than norepinephrine and NPY I the vasoconstrictor control of the cutaneous circulation, with particular emphasis on a potential role for ATP. [unreadable] [unreadable]